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Small Animal Medicine > Antifungal Therapy > Flashcards

Antifungal Therapy Flashcards

1
Q

What is the MOA of Amphotericin B?

A
  • Binds sterols in cell membrane of eukaryotes, increasing cell permeability and causing leakage of nutrients and electrolytes
    • Greater affinity for ergosterol (fungi) than cholesterol (humans)
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2
Q

What are some signs of acute Amphotericin B toxicity (ie. occurring during infusion)?

A
  • Fever
  • Vomiting
  • Mylagia
  • Anaphylaxis
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3
Q

Signs of acute amphotericin B toxicity are most commonly seen with what type of formulations? How can this be reduced?

A

Lipid; can be reduced by slowing infusion rate

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4
Q

What are some signs of chronic Amphotericin B toxicity?

A
  • NEPHROTOXICITY
    • ​dose-limiting, typically cumulative effect, can be reduced w/ some lipid forms
  • Weight loss
  • Non-regenerative anemia
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5
Q

What are some characteristics of the formulation Amphotericin deoxycholate (Fungizone)?

A
  • Not lipid complexed
  • Highly protein bound
  • Accumulates in liver, kidneys, and lungs - check renal values/USG
    • _​_Should be diluted with sterile H2O and D5W
  • Wide distributions in tissues and inflammatory exudates
  • Poor penetration: bones, brain, CSF, aqueous/vitreous humors, resp secretions, uninflamed body cavities
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6
Q

What are some characteristics of the formulation Amphotericin cholesteryl sulfate (Amphocil)?

A
  • Lipid complex
  • Taken up by macrophages
  • Highly concentrated in liver, spleen, lung (MPS organs)
  • Poor penetration: kidney, stomach, SI, bone marrow, brain/CSF
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7
Q

What are some characteristics of the formulation liposome encapsulated Amphotericin (AmBisome)?

A
  • Lipid complex
  • Taken up by macrophages to lesser extent (d/t small size)
  • Highly concentrated in liver, spleen, lung, kidney - high renal concentration
  • Best CSF penetration of amphotericin formulations
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8
Q

What are some characteristics of the formulation lipid complexed amphotericin (Abelcet)?

A
  • Lipid complex
  • Rapid uptake by MPS (large particle)​
  • Higher concentration in liver, spleen, lung
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9
Q

What is the spectrum for Amphotericin B?

A
  • Blasto
  • Histo
  • Crypto
  • Coccidiodies
  • Aspergillus (some resistance)
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10
Q

Why is Amphotericin B not as regularly used today? Why might you still reach for it?

A
  • Has been largely displaced by safer (less nephrotoxic) drugs
  • used in patients in which finances are limited (although safer, lipid-complexed forms are $$$ too)
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11
Q

Describe Flucytosine

A
  • Converted to fluorouracil w/in fungal organism (yeast) and interferes w/ DNA synthesis
  • Good oral absorption
  • Crosses BBB/CSF
  • Effective vs: Crypto and Candida
  • Ineffective vs. Aspergillus
  • Synergistic w/ amphotericin B
    • rapid resistance
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12
Q

What are the side effects of flucytosine?

A
  • Nephrotoxicity
  • Drug eruptions (dogs)
  • Thrombocytopenia? (cats)
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13
Q

Describe characteristics of azole derivatives

A
  • Inhibit sterol (via cP450), nucleic acid, trig, and fatty acid synthesis
  • ​generally less toxic than amphotericin B
  • Fungistatic at low concentrations, fungicidal at high concentrations (not achieveable systemically)
  • Hepatic metabolism (cytochrome P450) **drug interactions
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14
Q

Describe characteristics of ketoconazole

A
  • PO or topical
  • Variable oral absorption (improved w/ fatty meal/acid - NO antacids)
  • Protein bound
  • Good penetration of most tissues and body fluids
  • Poor penetration of CNS, eye, and seminal fluid
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15
Q

What are the side effects of ketoconazole?

A
  • Nausea/vomiting, decreased appetite (minimized w/ meals/divided doses)
  • Hepatotoxicity (usually reversible)
  • Occ. Thrombocytopenia
  • Anemia
  • Teratogenic
  • Cortisol suppression
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16
Q

What is the spectrum for ketoconazole?

A
  • Candida
  • Malassezia
  • Histo
  • Blasto
  • Coccidioides

**Less effective vs. Aspergillus, Crypto, Sporothrix

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17
Q

What are some concerns when treating with ketoconazole?

A
  • It has a very slow onset of action, so may need to treat severe dz w/ amphotericin B first
  • Relapses are common - treat at least 4 weeks beyond resolution of clinical dz
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18
Q

Describe itraconazole

A
  • PO or IV
  • Variable oral absorption
    • capsules (improved w/ fatty meal/acid)
    • oral solution (improved in fasted state)
    • DO NOT USE COMPOUNDED FORM
  • Protein bound
  • Good penetration of most tissues
  • Minimal excretion in urine
  • Poor CNS penetration
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19
Q

What are the side effects of itraconazole?

A
  • Less toxic than ketoconazole
  • Nausea, vomiting, inappetence
  • Hepatotoxicity
  • Ulcerative dermatitis
  • Does NOT suppress cortisol production
20
Q

What is the spectrum for itraconazole?

A
  • Histo
  • Blasto
  • Crypto
  • Coccidiodes
  • Aspergillus

Safest bet since is broad spectrum

21
Q

When do you stop treatment with itraconazole?

A

60 days beyond resolution of clinical dz

22
Q

Describe the characteristics of fluconazole

A
  • PO administration
  • Water soluble - high bioavailability
  • Not extensively bound
  • Good penetration of all body cavities and tissues INCLUDING CNS/CSF, eye
  • Minimal metabolism
  • RENAL excretion of active drug
23
Q

What are the side effects of fluconazole?

A

Vomiting and diarrhea

24
Q

Fluconazole is the drug of choice for what fungal agent?

A

Crypto - IF there’s ocular or CNS involvement

25
Q

What is the spectrum for fluconazole?

A
  • Crypto
  • Candida
  • Blasto*
  • Histo*
  • Minimal efficacy against Aspergillus

*less effective than itraconazole

26
Q

How long is treatment with fluconazole?

A

Treat until (crypto) serum antigen testing is negative (usually 2 mo beyond resolution of C/S —> avg. duration = 8 mo)

27
Q

Describe voriconazole

A
  • Derivative of fluconazole - more lipophilic
  • High bioavailability
  • Metabolized by liver
  • More potent than Flu/Itraconazole for:
    • ​Aspergillus
    • Crypto
    • Candida
28
Q

Describe Posaconazole

A
  • Analogue of itraconazole
  • Good oral bioavailability - better w/ a meal
  • SE: uncommon - V/D, incr liver enzymes
  • there’s an extended released form
  • VERY expensive
29
Q

What is the spectrum of posaconazole?

A
  • Candida
  • Blasto
  • Systemic aspergillus
  • Histo
  • Crypto
  • Malassezia

As good or better than Flu or Itra

30
Q

Describe Clotrimazole

A
  • Topical imidazole - Minimal absorption when used topically
  • Most commonly used for nasal Aspergillus infusion
    • also used for bladder/renal pelvis infusions (Candida cystitis, renal aspergillosis)
    • Caustic
  • SE: irritating, erythema, airway obstruction secondary to inflammation from carrier, may prolong barbiturate anesthesia
31
Q

Describe Enilconazole

A
  • Topical triazole
  • SE: irritation (when highly concentrated solutions used)
  • Used for nasal Aspergillus infusions
32
Q

Describe Terbinafine

A
  • Inhibits ergosterol synthesis
  • High concentrations in skin and nails
  • Low concentrations in the lung
  • High oral bioavailability (enhanced w/ fatty meal)
  • Hepatic metabolism; 70% renally excreted
33
Q

What are the side effects of terbinafine?

A
  • Vomiting, diarrhea
  • hepatotoxicity
  • neutropenia, pancytopenia
34
Q

What is the spectrum of terbinafine?

A
  • Hyphal organisms
    • Aspergillus
    • Sporothrix
    • Dermatophytes
    • Pythium?
  • Poorly effective vs. yeast or dimorphism organisms
    • ​Histo
    • Blasto
35
Q

What do cell wall synthesis inhibitors target?

A
  • Chitin
  • Chitosan
  • Glucan
  • Mannan

**polysaccharides making up fungal cell wall

36
Q

What is the MOA of echinocandins?

A

Inhibit gluconate synthesis

37
Q

Describe Caspofungin, Micafungin, and Anidulafungin

A
  • Glucan inhibitors
  • Low oral bioavailability
  • Hepatic metabolism
  • Effective against invasive candidiasis and Aspergillus (esp. resistant to AMB/triazoles)
  • May have some efficacy vs. pythium
  • SE: fever, urticaria, pruritus, V/D, incr liver enzymes
  • VERY expensive
38
Q

Describe mefenoxam

A
  • Agricultural fungicide - plant pathogen oomycetes
  • Inhibits RNA polymerase
  • Not available for dogs (yet)
39
Q

Itraconazole is the preferred 1st choice antifungal for which fungal organisms?

A
  • Blasto
  • Histo
  • Coccidiodes
  • Systemic Aspergillus
40
Q

Amphotericin B has poor penetration of what tissues?

A
  • Bones
  • Brain/CSF
  • Aqueous/vitreous humor
41
Q

Describe iodides

A
  • supersaturated solutions: Potassium iodide and sodium iodide
  • Sporothrix tx
  • Cats —> side effects can be severe
  • Not commonly used
42
Q

What are two examples of chitin synthesis inhibitors?

A

Lufenuron and Nikkomycin

  • questionable efficacy for dermatophytes and coccidiomycosis
  • no longer used
43
Q

Why is the University of Texas fungal drug panel not really worth it?

A
  • B/c it gives you the MIC, not the concentration required to KILL the organism
  • there’s no established breakpoints for antifungals (no CLSI criteria)
  • takes 2-4 weeks
  • $$$
44
Q

When might you consider using the U Texas fungal sensitivity test?

A
  • Systemic aspergillosis
  • Non-responsive infection
  • Minimal $$ constraints
45
Q

Describe griseofulvin

A
  • MOA: disrupts mitosis
  • Variable absorption - give with fatty meal
    • Ultramicrosize = incr absorption
  • Can be used to treat dermatophyosis with topical
46
Q

What are the side effects of griseofulvin?

A
  • vomiting, diarrhea
  • anorexia
  • bone marrow suppression
  • Teratogenic

Small Animal Medicine (4 decks)

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